Glucocorticoids inhibit the coordinated translation of α- and β-globin mRNAs in friend erythroleukemia cells

• Published in: Archives of biochemistry and biophysics Vol. 227; no. 2; pp. 542 - 551
• Main Authors: Papaconstantinou, John, Stewart, James A., Rabek, Jeffrey P., McClintock, Patrick R., Wong, Edith Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.1983
• Subjects: Animals; Cell Line; Dimethyl Sulfoxide - pharmacology; Globins - genetics; Glucocorticoids - pharmacology; Hemoglobins - biosynthesis; Isoelectric Focusing; Leukemia, Erythroblastic, Acute - metabolism; Mice; Protein Biosynthesis - drug effects; RNA, Messenger - metabolism
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/0003-9861(83)90483-6

The dimethylsulfoxide (Me 2SO)-mediated induction of hemoglobin synthesis in Friend erythroleukemia cells is inhibited by the glucocorticoids hydrocortisone, dexamethasone, and fluocinolone acetonide; hydrocortisone, at concentrations of 10 −5 to 10 −8 m inhibits by 90−30% and fluocinolone acetonide at concentrations of 10 −8 to 10 −11 m shows a greater than 90% inhibition. At these concentrations the hormones have no effect on cell growth or viability. In this study it has been shown that there is a group of proteins, including the a- and β-globins, whose regulation is associated with the induction of Friend erythroleukemia cell differentiation, and that the expression of some of these, in addition to α- and β-globin, is affected by glucocorticoids. The levels of α- and β-globin mRNAs are very close to fully induced levels and preclude transcription as a major site for glucocorticoid control. In addition, it has been shown that glucocorticoids inhibit the translation of α- and β-globin mRNAs, that the level of this inhibition is concentration dependent, and that the translation of β-globin mRNA is slightly more sensitive to inhibition than the translation of α-globin mRNA. It is concluded that, although the translation of α- and β-globin mRNA is a major site of inhibition by glucocorticoids, there is a detectable amount of α- and β-globin synthesized. Thus, part of this mechanism may involve a differential sensitivity of α- and β-globin mRNA translation which results in unequal amounts of globin synthesis and an overall more potent inhibition of hemoglobin formation.